The primary goal of these studies is to determine the interactions among the elements of idiotype-anti-idiotype (antigen receptor-anti-receptor) networks in the regulation of immune responses and to assess the interactions of different idiotypic networks specific for the same hapten. The major cross-reactive idiotype (CRIc) associated with the BALB/c antibody response to the p-azophenylarsonate (Ar) hapten has been resolved into two heterogeneous families of cross-reactive idiotypes that are unrelated to each other. The 5AF6 family is expressed in BALB/c, A/J and a number of other strains whereas the other family (3C6) seems to be unique to BALB/c mice. The 5AF6 family shares several idiotypes in common with the minor CRI associated with A/J anti-Ar response, but neither the BALB/c 5AF6 or 3C6 families share idiotypes with the major A/J CRIa. Expression of each of the anti-Ar idiotype families 5AF6, 3C6 and CRIa is regulated independently of each other; however, suppression of CRIa can cause enhanced 5AF6 expression in F1(A/KxBALB/c) mice. Amino acid sequencing of three 5AF6 family monoclonal anti-Ar is under way. Other studies under way or to be initiated soon are designed to: (1)\estimate the extent of the regulatory repertoire of anti-idiotypic specificities directed toward CRIc by studying numerous anti-idiotype specific hybridoma antibodies; (2)\analyze the detailed cellular requirements for the induction of idiotype-specific suppressor T cells, using viable CRIc-conjugated lymphoid cells as models for idiotype-bearing inducer cells; (3)\evaluate the contribution of Ig light chain variable regions (VL) in the induction of idiotype-specific suppression of CRIc(+) antibodies by studying a mouse strain that expresses the necessary Ig heavy chains (VH) but fails to express the necessary VL required for CRIc expression.